[Abstrct] More and more laboratory indicators including serum creatinine , serum cystatin C , urinary microalbumin, N-acetyl-beta-D-Glucosaminidase (NAG), kidney injury molecule 1 (KIM-1), neutrophil gelatinase-associated lipocalin (NGAL), interleukin 18 (IL-18) and L type fatty acid binding protein (L-FABP) are used to diagnose and monitor acute kidney injury (AKI).However, the clinical applicability and limitations of these indicators , as well as the detection effect factors and biological variation on the diagnosis and monitoring of AKI are very important , especially how to combine the detection effect factors and biological variation to interpret test result is attached great importance by the laboratory personnel .

The Summer internship program has been successfully carried out in the Center for Reproductive Medicine in Cleveland Clinic for six years (from 2008 to 2013). This program includes lecture, essay writing and experimental research. Until this year, this program has trained 109 stu-dents from United States and all over the world. The students have published 78 articles in SCI jour-nals. This program has a good reputation in the international reproductive medicine education area. The program provides students strong backgrounds of an internship experience, which is helpful to the students when they apply for high level medical school and residency qualification. At present, the students in China have a strong and urgent demand for the similar programs. Some high level medical schools of our country have the personnel and equipment base to carry out these programs. Medical schools can carry out similar programs in our country by using the organization and implementation experiences of Cleveland Clinic to provide high-level Chinese medical students with practice experi-ence out of the course education.

Objective To assess the efficacy and safety of insulin Lispro in type 1 or type 2 diabetic patients.Methods Forty diabetic patients were assigned to receive premeal insulin Lispro plus bedtime Neutral Protamine Hagedorn(NPH)insulin for 12 weeks.The following characters were compared between before and after treatment,including fasting plasma glucose(FPG),1 h and 2 h postprandial glucose(after a standardized meal),glycosylated hemoglobin(GHbA_1c)levels,total daily insulin dose and the number of hypoglycemic episodes.Results Thirty-nine subjects fulfilled the study.After 12 weeks of Lispro treatment,the levels of FPG and 1 h and 2 h postprandial glucose were decreased significantly,being 1.12 mmol/L,2.37 mmol/L and 1.92 mmol/L respectively;GHbA_1c was decreased by 1.45%(from 8.9% to 7.5%).The dose of insulin Lispro was not changed,compared with the dose of regular human insulin at baseline.The incidence of hypoglycemia was decreased from 19.5 every week at baseline to 9.8 every week with Lispro.Conclusion Insulin Lispro is an effective agent for good glucose control with fewer hypoglycemic episodes in diabetic patients.

Objective To study the altered expression of dopamine transporter (DAT) in substantia nigra and striatum in postmortem human brain of Parkinson’s disease (PD). Methods Immunoautoradiography was used to reveal DAT distribution in postmortem human brain. Results Strongly labeling signal of DAT was mainly found in the substantia nigra, the putamen and the caudate nucleus in controls. In contrast, it was drastically reduced in the putmen and the dorsolateral caudate nuclus in PD brains, but the ventromedial part of the caudate nucleus showed a significant sparing adjacent to the border of the lateral ventricle. In the substantia nigra, the ventral and the lateral parts of the substantia nigra showed an obvious decreasing of DAT and the reducing degree of DAT labeling signals in those regions is smaller than that in the putamen and the caudate nucleus. Quantitative analysis revealed that 90.9% and 66.7% of the labeling intensity of DAT were decreased in the putamen and the caudate nucleus as comparing with the corresponding controls respectively (P

Dysfunctional spermatozoa maturation is the main reason for the decrease in sperm motility and morphology in infertile men. Ejaculated spermatozoa from healthy fertile men were separated into four fractions using three-layer density gradient. Proteins were extracted and bands were digested on a LTQ-Orbitrap Elite hybrid mass spectrometer system. Functional annotations of proteins were obtained using bioinformatics tools and pathway databases. Western blotting was performed to verify the expression levels of the proteins of interest. 1469 proteins were identified in four fractions of spermatozoa. The number of detected proteins decreased according to the maturation level of spermatozoa. During spermatozoa maturation, proteins involved in gamete generation, cell motility, energy metabolism and oxidative phosphorylation processes showed increasing expression levels and those involved in protein biosynthesis, protein transport, protein ubiquitination, and response to oxidative stress processes showed decreasing expression levels. We validated four proteins (HSP 70 1A, clusterin, tektin 2 and tektin 3) by Western blotting. The study shows protein markers that may provide insight into the ejaculated spermatozoa proteins in different stages of sperm maturation that may be altered or modified in infertile men.

OBJECTIVE: To observe the effects of Jianpi Huoxue Decoction, a compound Chinese herbal medicine, on Kupffer cell signal pathway activation in rats with liver injury induced by Lieber-Decarli liquid diet and lipopolysaccharide (LPS). METHODS: SD rats were divided into normal, control liquid diet, ethanol liquid diet and ethanol liquid diet plus Jianpi Huoxue Decoction group. Rats were administrated with Jianpi Huoxue Decoction or distilled water via gastrogavage for 4 weeks after administration with ethanol or control liquid diet for 2 weeks respectively. After that, rats in each group were stimulated with LPS via gastrogavage for 3.5 h and harvested. Alanine aminotransferase (ALT) in serum and triglyceride (TG) in liver were analyzed. Pathological changes in liver tissues were observed in HE staining section. Tumor necrosis factor-alpha(TNF-alpha) in portal vein plasma was assayed by ELISA. The protein expressions of CD68, Toll-like receptor 4 (TLR4), phosphorylation-I kappa B (P-I kappa B) and TNF-alpha in liver were evaluated with Western-blotting. RESULTS: After the treatment with Jianpi Huoxue Decoction, the pathologic changes in liver tissue were lightened, levels of ALT in serum, TG in liver and TNF-alpha in portal vein plasma were decreased, and the protein expressions of CD68, TLR4, P-IkappaB and TNF-alpha in liver were reduced. CONCLUSION: Jianpi Huoxue Decoction can inhibit Kupffer cell signal pathway activation in rats with liver injury induced by Lieber-Decarli liquid diet and LPS.

OBJECTIVE: Duplicating the classical alcoholic hepatic injury model, to provide an ideal animal model for research on prevention and treatment of hepatic injury. METHODS: According to the prescription of Lieber-DeCarli, the same calorie fluid animal feed, which contained ethanol or non-ethanol, was prepared. Twenty-three rats were divided into normal control group (n=5), control liquid diet group (n=9), ethanol liquid diet group (n=9). Rats in the normal control group were fed normal diet, and rats in the control liquid diet group and ethanol liquid diet group were fed the corresponding diet for eight weeks. The pathologic changes of hepatic tissue were observed. The activities of the serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST), the liver tissue gamma-glutamyltransferase (gamma-GT), the content of triglyceride (TG), and the lipid peroxidation by-products were assayed. RESULTS: Compared to the normal control and the control liquid diet groups, the activities of ALT, AST, and gamma-GT, and the lipid peroxidation by-products increased significantly in the ethanol liquid diet group. The pathological changes of cellular swelling and fatty degeneration in the ethanol liquid diet group were severe. CONCLUSION: Alcoholic hepatic injury model can be successfully duplicated by Lieber-DeCarli prescription.

Objective To evaluate the efficacy and safety of sunitinib as first line treatment in patients with metastatic renal cell carcinoma (RCC). Methods This study included 46 Chinese patients who were diagnosed with metastatic RCC after radical nephrectomy. The patients received oral sunitinib (50 mg once daily on a 4 weeks on, 2 weeks off) on a 6 weeks cycle dose schedule until disease progression or intolerable toxicities occurred. Results The overall objective response rate was 32.6% (95% confidence interval [CI, 19.1% to 46. 1%]), and the disease control rate was 86.9%,with complete response (CR) 0 (0%), partial responses (PRs) 15 (32.6%), stable disease (SD) 25(54.3 %), and progression disease (PD) 6 ( 13. 1%). The median progression-free survival was 11 months, and the 1-year survival rate was 65.2%, while the median overall survival (mOS) has not been reached. The main adverse events included fatigue 33 (71.7%), skin discoloration 29 (63.0 %),anorexia 28 (60.9%), hand-foot syndrome 26 (56.5%), oral mucositis 25 (54.3%), hypertension 19 (41.3%), facial edema 18 (39.1%), diarrhea 17 (37.0%), hemorrhage 17 (37.0%), nausea 15 (32.6%), and hematological toxicity: leukopenia 32 (69.6%), neutropenia 30 (65.2%), thrombocytopenia 28 (60.9%), anemia 21 (45.7%). Most of grade 3/4 serious adverse events were thrombocytopenia in 15 (32. 6%) patients. Conclusions Sunitinib has a prominent effect in metastatic renal cell cancer in a Chinese population with mostly mild to moderate adverse reactions. More attention should be paid to grade 3/4 adverse reaction of thrombocytopenia.

Objective To explore the dynamic changes of diffusion tensor imaging(DTI) in spinal cord of goats with persistent compression injury. Methods Eighteen goats weighted 20--25 kg were divided into three groups with completely random design: A, B and C. A balloon catheter was inserted into the epidural space at C3-4 level via intervertabral foramen for each goat. The balloon was inflated by injection of variable volumes of saline in group A and B 10 days following operation. The volume of saline was 0. 3 ml in group A and 0. 2 ml in group B,respectively. The compression sustained for 40 days. Group C served as uncompressed control without injection of saline. The locomotor rating score was applied to each group. Conventional MRI and DTI were performed. The apparent diffusion coefficient (ADC)and fractional anisotropy (FA) values were measured. Histopathological assessments of the compressed spinal cord were performed 50 days following operation with light microscope and transmission electron microscopy. Results Before operation, the locomotor rating score was 5, the ADC value was ( 1.23 ± 0. 05 ) × 10-3 mm2/s and the FA value was (0. 72 ± 0. 05 ) each group. Of six goats in Group A, the locomotor rating score severely decreased and reached( 1.5±0. 4)on the 40 th day after compression. The ADC value at compression site decreased soon and reached the minimum (0. 75±0. 04) × 10-3mm2/s on the 5 th day after compression. Then the ADC value increased gradually, restored normal on the 10 th day or so, then became markedly higher than normal and reached( 1.61±0. 05) × 10-3mm2/s on the 40 th day. The FA value at compression site decreased soon, reached(0. 54±0. 04)on the 1st day, then decreased gradually and reached(0. 43 ± 0.05) on the 40 th day. It appeared high signal intensity on T2WI on the 10 th day. In Group B, the locomotor rating score was moderately decreased and reached(3.4±0. 5 )on the 40 th day. The ADC value at compression site decreased slightly firstly, reached( 1.08±0. 04) × 10-3mm2/s on the 1st day, restored normal on the 20 th day or so, then increased gradually, became higher than normal and reached ( 1.27 ± 0. 05) × 10-3mm2/s on the 40 th day. The FA value increased slightly firstly, reached (0. 78±0. 05 )on the 1st day, then decreased gradually, restored normal on the 15 th day or so, became lower than normal and reached(0. 67±0. 05) on the 40 th day. There was no abnormality on conventional MRI. In Group C, the locomotor rating score, ADC value and FA value remained unchanged. There was no abnormality on conventional MRI. There were dynamic changes over time of the ADC value and FA value in Group A and B, which was more marked in Group A than that in Group B ( repeated measurements analysis of variance, F=426. 7 for the ADC value and F =7895.2 for the FA value, P < 0. 01 ). Histopathologically, swelling and degeneration of axons and neurons as well as the disarrangement of myelin sheathes could be seen. The pathological changes were more marked in Group A than in Group B. In Group C, no abnormality could be seen. Conclusion There are dynamic changes of DTI in cervical spinal cord with compressive injury that correlated with the degree and duration of compression. The ADC value decreased firstly, restored normal and then increased. The FA value increased firstly, restored normal and then decreased in mild compression while solely decreased in serious compression.

Objective To explore the role of EphB4 in proliferation of glioma cells. Methods The mRNA and protein expressions of EphB4 were detected using RT-PCR, immunochemistry, and Western-blot, respectively. EphB4 siRNA was synthesized and transfected into U251 cells using Lipofectamine 2000. Glioma cell proliferation, apoptosis, and invasion were determined by MTT assay, TUNEL and transwell experiment, respectively. Results The expression (P<0.05) and proliferation of EphB4 were obviously decreased in U251 transfected with EphB4 siRNA and the proliferation was further decreased with the increased concetrations of siRNA. Compared with U251 group and siRNASCR group, EphB4 siRNA at different concentrations (25, 50 or 100 nmol/L) significantly reduced the invasion ability of cells and increased the number of apoptotic cells (P<0.05). Conclusions EphB4 plays an important role in the regulation of glioma cell proliferation, apoptosis and invasion.